Trkb or trkc agonist compositions and methods for the treatment of otic conditions

Abstract

Disclosed herein are compositions and methods for the treatment of otic diseases or conditions with TrkB or TrkC agonist compositions and formulations administered to an individual afflicted with an otic disease or condition, through direct application of these compositions and formulations onto or via perfusion into the targeted auris structure(s).

1 .- 26 . (canceled) 
     
     
         27 . An otic pharmaceutical composition, comprising:
 (i) a therapeutically effective amount of a TrkB agonist, wherein the TrkB agonist is an antibody or a binding fragment thereof comprising light chain complementarity-determining regions (CDRs) comprising SEQ ID NOs: 14-16 and heavy chain CDRs comprising SEQ ID NOs: 17-19;   (ii) between about 14% to about 21% by weight of a polyoxyethylene-polyoxypropylene triblock copolymer; and   (iii) water,   wherein the otic composition is formulated for intratympanic administration.   
     
     
         28 . The otic pharmaceutical composition of  claim 27 , wherein the antibody or a binding fragment thereof specifically binds to cells that express or overexpress TrkB. 
     
     
         29 .- 30 . (canceled) 
     
     
         31 . The otic pharmaceutical composition of  claim 27 , wherein the antibody or a binding fragment thereof is a monoclonal antibody, a diabody, a linear antibody, a single-chain antibody, a bi-specific antibody, a multispecific antibody formed from antibody fragments, a tandem antibody, a chimeric antibody, a murine antibody, a humanized antibody, a veneered antibody, a F(ab′)2 fragment, a Fab′ fragment, a Fab fragment, a Fv fragment, a Fc fragment, a rIgG fragment, or a scFv fragment. 
     
     
         32 . (canceled) 
     
     
         33 . The otic pharmaceutical composition of  claim 27 , further comprising two or more characteristics selected from:
 (i) between about 0.001% to about 60% by weight of the TrkB agonist;   (ii) sterile water, q.s., buffered to provide a pH between about 5.5 and about 8.0;   (iii) a gelation temperature between about 19° C. to about 42° C.; and   (iv) an apparent viscosity of about 100,000 cP to about 500,000 cP.   
     
     
         34 . (canceled) 
     
     
         35 . The otic pharmaceutical composition of  claim 27 , wherein the non-natural TrkC agonist binds to an epitope comprising the sequence as set forth in SEQ ID NO: 118. 
     
     
         36 . The otic pharmaceutical composition of  claim 27 , wherein the TrkB agonist is released from the composition for a period of at least 3 days. 
     
     
         37 . (canceled) 
     
     
         38 . The otic pharmaceutical composition of  claim 27 , wherein the pharmaceutical composition is an auris-acceptable thermoreversible gel. 
     
     
         39 . The otic pharmaceutical composition of  claim 27 , wherein polyoxyethylene-polyoxypropylene triblock copolymer comprises poloxamer 407, poloxamer 188, poloxamer 237, or poloxamer 338. 
     
     
         40 . The otic pharmaceutical composition of  claim 27 , wherein the composition has a gelation temperature of between about 19° C. to about 42° C. 
     
     
         41 . The otic pharmaceutical composition of  claim 27 , wherein the composition comprises between about 14% to about 17% by weight of a polyoxyethylene-polyoxypropylene triblock copolymer. 
     
     
         42 . A method of treating an otic condition in a subject, the method comprising administering to a subject in need thereof the otic pharmaceutical composition of  claim 27 . 
     
     
         43 . The method of  claim 42 , wherein the otic condition is selected from a group consisting of ototoxicity, chemotherapy induced hearing loss, excitotoxicity, sensorineural hearing loss, noise induced hearing loss, Meniere's Disease/Syndrome, endolymphatic hydrops, labyrinthitis, Ramsay Hunt's Syndrome, vestibular neuronitis, tinnitus, presbycusis, and microvascular compression syndrome. 
     
     
         44 . The method of  claim 43 , wherein administering the otic composition comprising the TrkB agonist treats sensorineural hearing loss by inducing auris neuronal cell growth. 
     
     
         45 . The method of  claim 42 , wherein the otic condition is characterized by damaged ribbon synapse, neurodegeneration, or synaptopathy.